The optic chiasm as a midline choice point

doi:10.1016/j.conb.2004.01.010

Current Opinion in Neurobiology

Volume 14, Issue 1, February 2004, Pages 51-60

https://doi.org/10.1016/j.conb.2004.01.010 Get rights and content

Abstract

The mouse optic chiasm is a model for axon guidance at the midline and for analyzing how binocular vision is patterned. Recent work has identified several molecular players that influence the binary decision that retinal ganglion cells make at the optic chiasm, to either cross or avoid the midline. An ephrin-B localized to the midline, together with an EphB receptor and a zinc-finger transcription factor expressed exclusively in the ventrotemporal retina where ipsilaterally projecting retinal ganglion cells are located, comprise a molecular program for the uncrossed pathway. In addition, the mechanisms for axon divergence in the optic chiasm are discussed in the context of other popular models for midline axon guidance.

Section snippets

Introduction: the biological function of the optic chiasm

Most animals with frontally located eyes have binocular vision, such that the central (binocular) portion of the visual field is perceived by both eyes and bilaterally processed in higher visual centers. The major functional consequence of this arrangement is depth perception, which in most mammals is established at the level of the optic chiasm. This X-shaped structure is actually a partial decussation, where axons from regions of retina that perceive each visual hemifield segregate together

Midline structures: are they all the same?

Although much has been learned about the factors that regulate crossing behavior at the midline through genetic analysis of the ventral nerve cord in Drosophila, it has become increasingly clear that these mechanisms are not necessarily conserved in the vertebrate spinal cord, nor indeed in other midline structures in higher vertebrates 3., 4., 5.. Anatomically, the chiasm differs from both the ventral nerve cord and spinal cord in that there is but a single population of commissural neurons,

The chiasm midline: cues for divergence

One of the first classes of molecules found to influence the uncrossed population in vivo are the chondroitin sulfate proteoglycans (CS-PGs), extracellular matrix proteins that are generally thought to be unfavorable for axon growth 28., 29.. In mouse, CS-PGs are expressed by the early population of neurons in the ventral diencephalon, and enzymatic removal of the chondroitin moieties has an age-dependent effect on RGC guidance 30., 31.. If treated at an early age (E13) when few retinal axons

EphB1, receptor for the uncrossed retinal projection, and its regulation

Given the number of EphB receptors present in the retina 40.••, 41., 42., 43., 44., it seems likely that many of them function redundantly. Indeed, this is the case for intraretinal guidance, as dorsal axons in EphB2; EphB3 double mutants overshoot the optic nerve head, but neither EphB2 nor EphB3 single mutants display a phenotype [42]. However, EphB1 appears to act alone with respect to midline guidance at the chiasm. Although its mRNA is expressed highly in ventral retina, EphB2 mutants have

Regulatory genes controlling the retinal axon projection at the chiasm midline

As we have seen, recent studies have shed light on the guidance molecules involved in the navigation of retinal axons at the optic chiasm. Less is known, however, about what controls the ability of individual retinal axons to express these specific guidance molecules. The emerging view in other models used to study neural identity and axon trajectory is that each neuronal subtype possesses an intrinsic capacity to detect its own unique path soon after it becomes postmitotic [52^•]. This ability

Conclusions

Progress has been made on understanding how the uncrossed pathways diverge from the crossed pathway, in Xenopus and in the mouse optic chiasm. Zic2 and EphB1 are both expressed concomitantly in the ventrotemporal retina, site of origin of the uncrossed RGCs. The results from gain- and loss-of-function experiments in vitro and in vivo strongly argue that this transcription factor and guidance receptor comprise major determinants of the uncrossed pathway, with ephrin-B2 as a key inhibitory ligand

Update

Recently, a report has described the generation of a neural-specific conditional knockout of the heparan sulfate (HS) polymerizing enzyme EXT1 (Nes-EXT1-null), which is essential for HS synthesis [71]. These mutants display multiple neural patterning defects in cell proliferation and commissure formation. In the optic chiasm of Nes-EXT1-null mice, many retinal axons aberrantly project into the contralateral optic nerve. This phenotype shows a genetic interaction with Slit2, which has been shown

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

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of special interest
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of outstanding interest

Acknowledgements

We wish to sincerely apologize to those colleagues whose work has contributed greatly to our thinking, and was not cited due to space limitations. We are grateful to the National Institutes of Health National Eye Institute (NEI-EY12736, T32 EY13933 and NINDs P030532), and the Human Frontiers Science Program for supporting the research conducted in our laboratory.

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